CN107533079B - Automatic analysis device and method - Google Patents

Automatic analysis device and method Download PDF

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Publication number
CN107533079B
CN107533079B CN201680022150.XA CN201680022150A CN107533079B CN 107533079 B CN107533079 B CN 107533079B CN 201680022150 A CN201680022150 A CN 201680022150A CN 107533079 B CN107533079 B CN 107533079B
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sample
nozzle
liquid
cleaning
container
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CN107533079A (en
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安居晃启
千田早织
平野匡章
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Hitachi High Tech Corp
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Hitachi High Technologies Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1004Cleaning sample transfer devices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016Control of the volume dispensed or introduced
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178Special arrangements of analysers
    • G01N2035/00237Handling microquantities of analyte, e.g. microvalves, capillary networks
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

The sample dispensing device is provided with a sample dispensing mechanism (12), wherein the sample dispensing mechanism (12) is provided with a sample nozzle (12a), the sample nozzle (12a) dispenses a sample in a sample container (15) into a reaction container (2) by sucking and discharging the sample as an analysis object, and the sample dispensing mechanism (12) is controlled to execute: a sample suction process of inserting the sample nozzle (12a) into the sample container (15) to suck the sample in the sample container (15); a liquid suction process for sucking liquid through the sample nozzle (12a) after the sample suction process; and a discharge process for discharging the liquid and a part of the sample from the sample nozzle (12a) to the empty reaction vessel (2) in the order of the liquid and the part of the sample. Thus, an automatic analyzer and method can be provided, which can dispense a minute amount of sample with high accuracy regardless of the shape of the sample nozzle or the viscosity of the sample.

Description

Automatic analysis device and method
Technical Field
The present invention relates to an automatic analyzer and a method for quantitatively and qualitatively analyzing a biological sample such as blood and urine.
Background
In order to quantitatively and qualitatively analyze a specific component contained in a biological sample (hereinafter, referred to as a sample) such as blood or urine, an automatic analyzer is indispensable for current diagnosis and the like because of high reproducibility of an analysis result and a high processing speed.
As a measurement method used in an automatic analyzer, there is known a method in which: the analysis is performed by dispensing a sample contained in a sample container and a reagent contained in a reagent container into a reaction container and mixing them with each other by a dispensing device or the like, using an analysis method (colorimetric analysis) using a reagent in which the color of a reaction solution changes by reacting with an analysis target component in a sample, or an analysis method (immunoassay) using a reagent in which a labeled substance is added to a substance that specifically binds to an analysis target component in a sample directly or indirectly, and the labeled substance is counted.
In such an analysis, as a sample container for storing a sample, in addition to an open type sample container having an opening at an upper portion, a vacuum blood collection tube or the like having an opening end sealed with a plug or the like and having its interior depressurized is sometimes used as a sample container, and various sample dispensing methods have been studied.
As a technique for dispensing a sample from a sample container that is plugged like a vacuum blood collection tube, for example, patent document 1 (japanese patent application laid-open No. 4-252960) discloses a sampling device including: a sample carrier for moving the plurality of sample containers to a sampling position; a lateral translator provided to have a movement path in the sampling position information; a vertical direction translator installed in a manner of being located laterally by the lateral translator; a sampling probe that is moved in the vertical direction into and out of the sample container by a vertical direction translator; a liquid pump connected to the probe in such a manner as to aspirate a sample from the sample container; a controller unit for operating the two translators and the pump to perform the aspiration operation, the sampling device being characterized in that the two translators are flow-driven actuators, the sample container is upright and at least one sample container is closed.
Documents of the prior art
Patent document
Patent document 1 Japanese patent application laid-open No. 4-252960
Disclosure of Invention
Problems to be solved by the invention
In recent years, demands for improvement in throughput of automatic analyzers, reduction in analysis cost, and the like have been increasing, and there is a demand for reduction in the amount of reagents used in the above-described analysis method in which reagents are added to a sample. Therefore, the sample used for one-time analysis in the automatic analyzer is required to be on the order of one-digit microliter, and high dispensing accuracy is required.
On the other hand, in the case where a sample is directly collected without being uncapped from a sample container such as a vacuum blood collection tube sealed with a plug or the like from an open end as in the conventional art, since a sample nozzle of a dispensing device directly penetrates the plug or the like and is immersed in the sample container, it is necessary to consider an insertion load acting on the sample nozzle. Therefore, the sample nozzle for penetrating the rubber stopper or the like of the closed sample container needs to have a sharp tip shape by increasing the outer diameter and reducing the insertion load to the rubber stopper or the like, compared to the sample nozzle used for the open sample container.
However, when the outer diameter of the sample nozzle is large or the tip is sharp, the discharge momentum is reduced due to the large opening of the sample nozzle, and the sample is difficult to separate from the tip of the sample nozzle because the opening must be inclined with respect to the bottom surface of the reaction vessel. In particular, when a sample having a high viscosity such as whole blood or blood cells subjected to centrifugal separation is dispensed, it is very difficult to wet and spread the sample on the bottom surface of the reaction container, and there is a problem that the sample is carried back when the sample nozzle is detached from the reaction container.
The present invention has been made in view of the above problems, and an object of the present invention is to provide an automatic analyzer and an automatic analyzing method capable of dispensing a minute amount of sample with high accuracy regardless of the outer shape of a sample nozzle or the viscosity of the sample.
Means for solving the problems
In order to achieve the above object, the present invention includes: a sample dispensing mechanism having a sample nozzle for dispensing a sample in a sample container to a reaction vessel by sucking and discharging the sample to be analyzed; and a control unit that controls the sample dispensing mechanism to execute: the method includes a sample suction process of inserting the sample nozzle into the sample container to suck the sample in the sample container, a liquid suction process of sucking a liquid through the sample nozzle after the sample suction process, and a discharge process of discharging the liquid and a part of the sample from the sample nozzle to the empty reaction container in this order of the liquid and the part of the sample.
Effects of the invention
According to the present invention, a minute amount of sample can be dispensed with high accuracy regardless of the shape of the sample nozzle or the viscosity of the sample.
Drawings
Fig. 1 is a diagram schematically showing the overall configuration of an automatic analyzer according to a first embodiment.
Fig. 2 is a schematic diagram showing the second sample dispensing mechanism being extracted.
Fig. 3 is a vertical sectional view schematically showing the cleaning tank, the liquid supply unit, and the water droplet removing unit by being drawn out.
Fig. 4 is a diagram showing a flow of a sample dispensing operation in the first embodiment.
Fig. 5 is a flowchart showing details of the sample dispensing operation in the first embodiment.
Fig. 6 is a vertical sectional view schematically showing the cleaning tank, the liquid supply unit, and the water droplet removing unit in the second embodiment.
Detailed Description
Embodiments of the present invention will be described with reference to the accompanying drawings.
< first embodiment >
A first embodiment of the present invention will be described in detail with reference to fig. 1 to 5.
Fig. 1 is a diagram schematically showing the overall configuration of an automatic analyzer according to the present embodiment.
In fig. 1, the automatic analyzer 100 is mainly composed of the following components: a sample container 15 for containing a sample to be analyzed; a sample rack 16 on which one or more sample containers 15 are mounted; a sample transport mechanism 17 for transporting the sample rack 16; a reagent bottle 10 containing a reagent for sample analysis; a reagent disk 9 in which a plurality of reagent bottles 10 are arranged in a circumferential direction; a reaction vessel 2 for mixing a sample and a reagent and reacting them; a reaction disk 1 in which a plurality of reaction containers 2 are arranged in a circumferential direction; first and second sample dispensing mechanisms 11 and 12 for dispensing a sample from a sample container 15 transported to a sample dispensing position by a sample transport mechanism 17 into a reaction container 2; reagent dispensing mechanisms 7 and 8 for dispensing a reagent from a reagent bottle 10 into the reaction vessel 2; stirring mechanisms 5 and 6 for stirring a mixed solution (reaction solution) of the sample and the reagent dispensed into the reaction container 2; a spectrophotometer 4 for measuring the absorbance of the reaction solution by measuring the transmitted light obtained from the reaction solution in the reaction vessel 2 from a light source not shown; a cleaning mechanism 3 for cleaning the used reaction vessel 2; a control unit 21 for controlling the overall operation of the automatic analyzer 100. The spectrophotometer 4 measures the absorbance of the mixed solution (reaction solution) to analyze the automatic analyzer 100. From the absorbance, the concentration of a predetermined component of the analysis item corresponding to the reagent can be calculated. In fig. 1, the connections between the respective mechanisms constituting the automatic analyzer 100 and the control unit 21 are partially omitted for the sake of simplicity of illustration.
The sample container 15 mounted on the sample rack 16 to be transported by the sample transport mechanism 17 includes: a closed sample container (plug container) having an opening at the upper part and having a lid member 86 such as a plug for closing the upper opening, and an open sample container (plug-opening container) having an opening by removing the lid member of the upper opening.
The first sample dispensing mechanism 11 has a sample nozzle 11a disposed with its tip directed downward, and a sample pump 19 is connected to the sample nozzle 11 a. The first sample dispensing mechanism 11 is configured to be capable of performing a rotation operation and a vertical operation in the horizontal direction, and is configured to dispense a sample from a sample container 15 to a reaction container 2 by inserting the sample nozzle 11a into an open sample container 15 to suck the sample and inserting the sample nozzle 11a into the reaction container 2 to discharge the sample. The first sample dispensing mechanism 11 inserts the sample nozzle 11a into the reaction vessel 2 to suck a sample (or a reaction solution) and discharges the sample (or the reaction solution) into another reaction vessel 2, thereby dispensing the sample (or the reaction solution) between the reaction vessels 2. A cleaning tank 13 for cleaning the sample nozzle 11a with cleaning water is disposed in the operating range of the first sample dispensing mechanism 11.
Fig. 2 is a schematic diagram showing the second sample dispensing mechanism being extracted.
As shown in fig. 2, the second sample dispensing mechanism 12 includes an arm 42 disposed to extend in the lateral direction, a sample nozzle 12a disposed at one end of the arm 42 with its tip directed downward, and an arm drive mechanism 41 disposed at the other end of the arm 42 and configured to perform a rotation operation and a vertical operation of the arm 42 in the horizontal direction. The sample nozzle 12a is connected to the syringe pump 51 through a pipe (not shown) provided through the arm drive mechanism 41, and is driven by the syringe pump drive mechanism 51 a. A pump 53 is connected to the syringe pump 51, the pump 53 supplies system water 74 such as pure water stored in the water tank 81 to the syringe pump 51 and the sample nozzle 12a, and an electromagnetic valve 52 for opening and closing (switching between flow and cutoff) a pipe is provided in a pipe connecting the pump 53 and the syringe pump 51.
The lower end of the sample nozzle 12a is formed into an acute angle (for example, the angle α between the axial direction of the sample nozzle 12a and the tip of the sample nozzle 12a is about 15 ° to 20 °) and is configured as a lid member that can penetrate the sealed sample container 15. That is, the second sample dispensing mechanism 12 inserts the sample nozzle 12a into the open-type sample container 15 or the closed-type sample container 15 to suck the sample, and inserts the sample nozzle 12a into the reaction container 2 to discharge the sample, thereby dispensing the sample from the sample container 15 into the reaction container 2.
Within the operating range of the second sample dispensing mechanism 12 are disposed: a washing tank 14 for washing the sample nozzle 12a with washing water; a liquid supply unit 71 which stores a liquid such as system water (pure water or the like) sucked by the sample nozzle 12a and is disposed at a liquid suction position; a water drop removing part 72 which removes water drops attached to the outer wall of the sample nozzle 12a and is disposed at the vacuum suction position.
Fig. 3 is a vertical sectional view schematically showing the cleaning tank, the liquid supply unit, and the water droplet removing unit by being drawn out.
As shown in fig. 3, washing tub 14 is provided with washing nozzle 73, and washing nozzle 73 discharges system water 74 stored in water tank 81 and supplied by pump 79 as washing water to wash sample nozzle 12 a. Further, a solenoid valve 77 for opening and closing (switching between flow and cutoff) a pipe is provided in a pipe connecting the pump 79 and the cleaning nozzle 73. In washing tank 14, the washing water discharged from washing nozzle 73 passes through the washing position where sample nozzle 12a is washed, and is discarded to a waste liquid tank (not shown) through waste liquid port 78 provided below the washing position.
The system water 74 stored in the water tank 81 is supplied to the liquid supply unit 71 by the pump 79, and a solenoid valve 75 for opening and closing (switching between flow and cutoff) a pipe is provided in a pipe connecting the liquid supply unit 71 and the pump 79. The liquid supply section 71 is disposed adjacent to the cleaning tank 14, and part of the system water 74 is discharged from a discharge section 71a provided on the cleaning tank 14 side of the liquid supply section 71 to a cleaning position of the cleaning tank 14.
The water droplet removing unit 72 is connected to a vacuum pump 80, and a solenoid valve 76 for opening and closing (switching between flow and interruption) the pipe is provided in a pipe connecting the water droplet removing unit 72 and the vacuum pump 80. In the water droplet removing unit 72, the water droplets sucked from the outer wall of the sample nozzle 12a are discarded to a waste liquid tank (not shown) via the vacuum pump 80.
The reagent dispensing mechanisms 7 and 8 are connected to the reagent pump 18, the cleaning tanks 32 and 33 are disposed within the operating ranges of the reagent dispensing mechanisms 7 and 8, and the cleaning tanks 32 and 33 clean the reagent nozzles 7a and 8a of the reagent dispensing mechanisms 7 and 8. In addition, cleaning tanks 30 and 31 for cleaning the stirring mechanisms 5 and 6 are disposed in the operating ranges of the stirring mechanisms 5 and 6. A cleaning pump 20 is connected to the cleaning mechanism 3.
The control unit 21 controls the overall operation of the automatic analyzer 100 including the pumps 18 to 20, 53, 79, 80, the solenoid valves 52, 75 to 77, the drive mechanisms 41, 51a, and the like, performs a sample dispensing operation described later, and analyzes the sample based on the measurement result from the spectrophotometer 4.
Here, the dispensing operation in the present embodiment will be described with reference to fig. 4 and 5.
Fig. 4 is a diagram showing a flow of a sample dispensing operation in the present embodiment. Fig. 4 shows a case where a sample is dispensed from the sealed sample container 15 into the reaction container 2.
In the dispensing operation, first, the arm drive mechanism 41 drives the arm 42 to move the sample nozzle 12a to the cleaning position of the cleaning bath 14, and the solenoid valves 52 and 77 are caused to flow (opened) to discharge the system water 74 from the cleaning nozzle 73 and the sample nozzle 12a, thereby cleaning the outside and inside of the sample nozzle 12a and filling the sample nozzle 12a with the system water 89 (state (a)). At this time, the sample at the time of the previous sample dispensing operation, waste 94 such as air-saving waste, and the like are discarded. After the cleaning of the sample nozzle 12a is completed, the solenoid valves 52 and 77 are turned off (closed).
Next, the sample nozzle 12a is moved to the vacuum suction position, the electromagnetic valve 76 is opened, and the water droplet 82 on the outer wall of the sample nozzle 12a is removed by the water droplet removing unit 72 (state (b)). The solenoid valve 76 is closed after the water droplets on the outer wall of the sample nozzle 12a are removed.
Next, the sample nozzle 12a is moved to the outside of the vacuum suction position, the syringe pump 51 is driven by the syringe pump drive mechanism 51a, and the air-saving 83 (volume V1) is sucked to the tip of the sample nozzle 12a (state (c)).
Next, the sample nozzle 12a is lowered from above the sealed sample container 15, the sample nozzle 12a is inserted into the sample container 15 through the lid member 86 (for example, a plug) of the sealed sample container 15, and the syringe pump 51 is driven to suck the sample 85 (volume V2) in a state where the sample nozzle 12a is immersed in the sample 84 in the sample container 15 (state (d)). The volume V2 is larger than the amount of sample actually discharged to the reaction container 2 for analysis.
Next, the sample nozzle 12a is pulled out from the lid member 86 and detached from the sample container 15 (state (e)).
Next, the sample nozzle 12a is moved to the cleaning position of the cleaning tank 14, the electromagnetic valve 77 is opened, and the system water 74 is discharged from the cleaning nozzle 73, and the outside of the sample nozzle 12a is cleaned (state (f)). At this time, the syringe pump 51 is driven to suck the system water 88 to the tip of the sample nozzle 12a (volume V3).
Next, the sample nozzle 12a is moved to the liquid suction position, immersed in the system water 74 stored in the liquid supply unit 71, and the syringe pump 51 is driven to suck additional system water 90 (volume V4) to the tip of the sample nozzle 12a (state (g)). Thereafter, the sample nozzle 12a is detached from the liquid supply portion 71. After the sample nozzle 12a is detached from the liquid supply unit 71, the electromagnetic valve 75 is opened for a predetermined time, the system water 74 is supplied to the liquid supply unit 71, the system water 74 in the liquid supply unit 71 is replenished, and the system water 74 is discharged from the discharge unit 71a to replace the system water 74 in the liquid supply unit 71. Further, since the system water 88 sucked in advance is present at the tip of the sample nozzle 12a in the state (f), a dispensing error caused by the diffusion of the sample 85 in the sample nozzle 12a into the system water 74 of the liquid supply unit 71 can be prevented. Further, since the system water 74 in the liquid supply section 71 is replaced after the sample nozzle 12a is detached from the liquid supply section 71, it is possible to prevent a small amount of sample components remaining on the outer wall of the sample nozzle 12a or the like from remaining in the system water 74 in the liquid supply section 71.
Next, the sample nozzle 12a is moved to the vacuum suction position, the electromagnetic valve 76 is opened, and the water droplet 82 on the outer wall of the sample nozzle 12a is removed by the water droplet removing unit 72 (state (h)). The solenoid valve 76 is closed after the water droplets on the outer wall of the sample nozzle 12a are removed. In the present embodiment in which a sample of about 1uL is dispensed, the inner diameter of the sample nozzle 12a is 1mm or less, whereas the distance between the outer wall of the sample nozzle 12a and the inner wall of the water droplet removing unit 72 is about several millimeters in order to avoid the risk of collision or the like. Therefore, the liquid such as system water and the sample in the sample nozzle 12a is prevented from being sucked by the suction force of the vacuum pump 80.
Next, the sample nozzle 12a is moved to the outside of the vacuum suction position, the syringe pump 51 is driven by the syringe pump drive mechanism 51a, and the air 91 (volume V5) is sucked into the tip of the sample nozzle 12a (state (i)). Since the air 91 is used as an acceleration section for increasing the discharge speed of the sample 85 before the sample is discharged into the reaction container 2, the volume V5 of the air 91 may be sufficient for accelerating the sample. The volume V5 is about 2 μ L, and the air 91 is sucked by sucking the system water 90 by about 15 mm.
Next, the sample nozzle 12a is inserted into the reaction vessel 2, and the air 91, the system water 90, the system water 88, and the sample 92 (volume V6) reference of a part (state (i)) of the sample 85 are discharged in this order by the syringe pump 51 in a state where the tip of the sample nozzle 12a is slightly in contact with the bottom surface of the empty reaction vessel 2 (state (j)). After the system water 90, 88 (volume V3+ V4) and a part of the sample 85 (volume V6) are discharged, the sample nozzle 12a is detached from the reaction vessel 2 and moved to the cleaning position of the cleaning tank 14 (i.e., switched to state (a)). Thereafter, the dispensing operation is repeated as necessary in accordance with the states (a) to (j).
Further, the system water 88, 90 and the sample 85a are accelerated when the air 91 (volume V5) is discharged in the state (j). When the velocities of the system water 88, 90 and the sample 85 are sufficiently increased, the system water 88, 90 first flies out from the tip of the sample nozzle 12 a. The system water 88, 90 has low viscosity and is therefore likely to wet and spread when in contact with the bottom surface of the reaction vessel 2, and the liquid inside the sample nozzle 12a and the bottom surface of the reaction vessel 2 are connected via the system water 88, 90. Thereafter, the sample 92 for analysis is continuously ejected from the tip of the sample nozzle 12a (volume V6). Since the liquid such as the sample in the sample nozzle 12a is already connected to the bottom surface of the reaction well 2 by the system water 88, 90 when the sample 92 flies out, the sample 92 is reliably wetted and spread (the mixture 93 of the sample 92 and the system water 88, 90) on the bottom surface of the reaction well 2 together with the system water 88, 90 even when the viscosity of the sample 92 is high, and therefore, the sample 92 is prevented from being carried back when the sample nozzle 12a is detached from the reaction well 2. Further, since the sample 95 (volume V7) remains in the sample nozzle 12a, the air 83 and the system water 89 are prevented from being blown out into the reaction container 2.
Although fig. 4 illustrates a case where a sample is dispensed from the sealed sample container 15 into the reaction container 2, the same dispensing operation can be performed in accordance with the states (a) to (j) even when a sample is dispensed from the open sample container 15 into the reaction container 2.
Fig. 5 is a flowchart showing details of the sample dispensing operation in the present embodiment.
In fig. 5, first, the control unit 21 controls the arm driving mechanism 41 to move the sample nozzle 12a to the front of the washing nozzle 73 at the washing position of the washing bath 14 (step S10), and opens the electromagnetic valves 52 and 77 to discharge the system water 74 from the washing nozzle 73 and the sample nozzle 12a for washing. When the sample or waste 94 such as air in the previous dispensing operation remains in the sample nozzle 12a, the waste 94 is discarded. In this cleaning step, the outside and the inside of the sample nozzle 12a are cleaned, and the sample nozzle 12a is filled with the system water 89 (step S20). Thereafter, the electromagnetic valves 52, 77 are closed (step S25).
Next, the sample nozzle 12a is moved to the vacuum suction position (step S30), the electromagnetic valve 76 is opened, and the water droplets 82 on the outer wall of the sample nozzle 12a are removed by the water droplet removing unit 72 (step S40). Thereafter, the electromagnetic valve 76 is closed (step S45).
Next, the sample nozzle 12a is moved out of the vacuum suction position from the vacuum suction position (step S50), and the air-throttle 83 is sucked into the tip of the sample nozzle 12a (step S60).
Next, the sample nozzle 12a is inserted into the sample container 15 (step S70), and the sample 85 is sucked (step S80).
Next, the sample nozzle 12a is detached from the sample container 15 (step S90), and the sample nozzle 12a is moved to the cleaning position in front of the cleaning nozzle of the cleaning bath 14 (step S100).
Here, it is determined whether or not the outer wall of the sample nozzle 12a needs to be cleaned according to the operation conditions of the dispensing operation (hereinafter, referred to as dispensing operation conditions) set in advance in the control unit 21 (step S110), and if the determination result is yes, the electromagnetic valve 77 is opened to discharge the system water 74 from the cleaning nozzle 73, and the outside of the sample nozzle 12a is cleaned (step S120). Next, it is determined whether or not the system water 88 needs to be sucked into the tip of the sample nozzle 12a according to the dispensing operation conditions (step S130), and if the determination result is yes, the system water 88 is sucked into the tip of the sample nozzle 12a (step S140). The case where it is determined in steps S110 and S130 that the sample nozzle cleaning and the suction of the system water 88 are not necessary (that is, the determination result in steps S110 and S130 is "no") is a case where it is known in advance that the viscosity of the sample to be dispensed contained in the sample container 15 is low (for example, the sample is not whole blood but is hemolyzed manually), and a case where the amount of the sample to be dispensed is relatively large (for example, about 10 uL). In addition, there may be a case where the sample nozzle cleaning is required and the suction of the system water 88 is not required. For example, in the case of manual hemolysis, the sample adhered to the periphery of the sample nozzle 12a is dropped, but the viscosity of the sample is low, and therefore, it is not necessary to suck the system water. How the sample flows can be realized by determining dispensing operation conditions in advance and determining whether or not the sample to be analyzed satisfies the conditions.
If the determination result in steps S110 and S130 is "no" or if the processing in step S140 is finished, it is determined whether or not it is necessary to move the sample nozzle 12a to the liquid suction position (step S150), and if the determination result is "yes", the sample nozzle 12a is moved to the liquid suction position (step S160). Next, it is determined whether or not the system water 90 needs to be sucked into the tip of the sample nozzle 12a according to the dispensing operation conditions (step S170), and if the determination result is yes, the system water 90 is sucked into the tip of the sample nozzle 12a (step S180). Note that the case where the system water 90 does not need to be sucked in step S170 (that is, the determination result in step S180 is "no") is a case where it is known in advance that the viscosity of the sample to be dispensed contained in the sample container 15 is low (for example, the sample is not whole blood but is hemolyzed manually), or a case where the sample dispensing amount is relatively large (for example, about 10 uL).
When the determination results in steps S150 and S170 are "no" or when the processing in step S180 is finished, it is determined whether or not the speed at which the sample nozzle 12a is separated from the liquid suction position is high (high-speed separation) according to the dispensing operation conditions (step S190), when the determination result is "yes", the sample nozzle 12a is separated from the liquid suction position at high speed (step S201), and when the determination result is "no", the sample nozzle 12a is separated from the liquid suction position at a low speed to such an extent that water droplets on the outer wall of the sample nozzle 12a can be removed (step S202). This enables the amount of water droplets on the outer wall of the sample nozzle 12a to be controlled. For example, if there is a step of removing water droplets in step 230 described later, the moving speed of the sample nozzle 12a is prioritized over the control of the amount of water droplets. On the other hand, if the step of removing water droplets in step 230, which will be described later, is not performed, the moving speed of the sample nozzle 12a can be set to a low speed in order to prioritize the removal of water droplets in step 202.
When the processing in steps S201 and S202 is completed, it is next determined whether or not the sample nozzle 12a needs to be moved to the vacuum suction position according to the dispensing operation conditions (step S210), and when the determination result is yes, the sample nozzle 12a is moved to the vacuum suction position (step S220), the electromagnetic valve 76 is opened, the water droplets 82 on the outer wall of the sample nozzle 12a are removed by the water droplet removing unit 72 (step S230), and thereafter the electromagnetic valve 76 is closed (step S235), and the sample nozzle 12a is moved out of the vacuum suction position from the vacuum suction position (step S240).
If the determination result in step S210 is "no" or if the processing in step S240 is finished, it is determined whether or not it is necessary to suck the air 91 to the tip of the sample nozzle 12a in accordance with the dispensing operation condition (step S250), and if the determination result is "yes", the air 91 is sucked to the tip of the sample nozzle 12a (step S260). If the determination result in step S250 is "no" or if the process in step S250 is completed, the sample nozzle 12a is moved (inserted) into the reaction container 2 に (step S270), the sample is discharged into the reaction container 2 (step S280), and the process returns to step S10.
Next, a specific example will be explained. The case where the sample nozzle 12a discharges a small amount of whole blood or previously hemolyzed manual hemolysis into the reaction vessel will be described. The device can recognize such distinction by, for example, identification information such as a barcode attached to the sample container or identification information such as a barcode attached to the sample rack 16. The flow of fig. 5 is determined according to the identification information and the dispensing operation conditions, and the dispensing operation of the sample nozzle 12a is performed according to the determined flow.
In the case of a small amount of whole blood, the flow proceeds to yes in steps S110, S130, S150, S170, S190, and S250 according to the flow of fig. 5. This can solve the problem of bringing back the sample when the sample nozzle 12a is detached from the reaction vessel. Even a trace amount of whole blood can be obtained by omitting a part of the steps as described later, and at least either of the steps S140 and S180 is necessary. That is, in the case of whole blood, the control unit controls the second sample dispensing mechanism 12 to perform: the sample suction (sample suction process) in step S80, the suction (liquid suction process) of the system water in any one of steps S140 and S180, and the sample discharge (sample discharge process) in step S280.
On the other hand, in the case of manual hemolysis, the flow of fig. 5 is yes in steps S110 and S150, and no in steps S130, S170, S190, S210, and S250. This is because, particularly in the case of manual hemolysis, the problem of bringing back the sample is not likely to occur. The system water suction (liquid suction process) in either of steps S140 and S180 can be omitted. That is, in the case of manual hemolysis, it is preferable that the control unit controls the second sample dispensing mechanism 12 to discharge a part of the sample to the reaction vessel without performing the system water suction (liquid suction process) in S140 and S180.
Next, the gist of the present embodiment will be explained. As described above, it is important to solve the problem of carry-over in a small amount of whole blood (for example, 5. mu.L or less). Therefore, after the sample is sucked by the sample nozzle 12a (after the sample suction process), a liquid having a viscosity or specific gravity lower than that of the sample is sucked by the sample nozzle (liquid suction process), and the liquid and a part of the sample are discharged from the sample nozzle to an empty reaction vessel in this order (discharge process). The liquid reliably wets and spreads at the bottom of the empty reaction vessel and connects the bottom of the reaction vessel to a part of the sample, so that the part of the sample can be discharged to the bottom of the reaction vessel without being carried back.
The liquid may be supplied from any position as long as it can be sucked before the suction of the sample and before the discharge. For example, it is conceivable to perform suction from the liquid reservoir. Alternatively, it is conceivable to suck the cleaning liquid discharged from the cleaning nozzle. The former has an advantage that the amount of liquid sucked from the reservoir is stable. On the other hand, the latter has an advantage that the liquid can be sucked without being brought close to the reservoir and the liquid can be sucked relatively in a short time, because the stability of the liquid suction amount is insufficient by sucking the flowing cleaning liquid, but the liquid can be sucked at the cleaning timing of the sample nozzle. It is contemplated that the liquid may be drawn from any location. However, the present invention is not limited to suction from these two positions. The amount of the liquid is, for example, about 1. mu.L.
In addition, the second point is air suction in step S260. That is, it is preferable to perform air suction (air suction processing) in addition to the liquid suction, and to discharge the liquid together with air when discharging the sample. Although the problem of bringing back the sample can be greatly improved without performing air suction, reliability can be improved by performing air suction. This is because a run-up distance for increasing the discharge speed of the liquid and the sample is generated when the liquid is discharged, and the discharged sample itself is easily separated from the tip of the sample nozzle.
In addition, the third point is the system water suction divided into two times of steps S140 and S170. In this case, the system water suction in step S170 corresponds to the liquid suction (corresponds to the liquid suction process). On the other hand, step S140 has a different role from the above-described bring-back problem. As described in the above-described state (f), the sample can be prevented from diffusing into the system water in the liquid supply portion 71. This prevents a dispensing error caused by diffusion. Therefore, it is preferable to perform the system water suction by dividing the water flow into two times.
However, in this case, the first system water does not necessarily have to be sucked. That is, a small amount of water may be introduced (added) to the tip of the sample nozzle 12a without suction. In this case, step S140 may be replaced with a cleaning water introduction process for introducing system water (cleaning water) into the sample nozzle, instead of the liquid suction process. For example, as a method of introducing water, in addition to direct suction, a sample may be slightly sucked, and an empty space may be provided in the sample nozzle 12a to fill the space with system water (washing water) discharged from the washing nozzle.
The operational effects of the present embodiment configured as described above will be described.
In the case where a sample is directly collected without opening a plug from a sample container such as a vacuum blood collection tube sealed with a plug or the like from an opening end, since a sample nozzle of a dispensing device directly penetrates the plug or the like and is immersed in the sample container, an insertion load acting on the sample nozzle needs to be considered. Therefore, the sample nozzle for penetrating the rubber stopper or the like of the closed sample container needs to have a sharp tip shape by increasing the outer diameter and reducing the insertion load to the rubber stopper or the like, compared to the sample nozzle for the open sample container.
However, when the sample nozzle has a large outer diameter and a sharp tip, the opening of the sample nozzle is large, and the discharge momentum is reduced, and the opening must be inclined with respect to the bottom surface of the reaction vessel, so that the sample is difficult to separate from the tip of the sample nozzle. In particular, when a sample having a high viscosity such as whole blood or a centrifuged blood cell is dispensed, it is very difficult to wet and spread the sample on the bottom surface of the reaction vessel, and there is a problem that the sample is carried back when the sample nozzle is detached from the reaction vessel.
In contrast, in the present embodiment, the configuration is such that: when a sample to be analyzed is dispensed by the sample nozzle 12a, the sample nozzle 12a sucks the washing water discharged from the washing nozzle of the washing tank 14 as necessary, or the sample nozzle 12a sucks the liquid in the liquid supply unit 71 as necessary, and discharges the liquid and a part of the sample in order from the sample nozzle 12a to the reaction container 2, so that a minute amount of the sample can be dispensed with high accuracy regardless of the outer shape of the sample nozzle 12a and the viscosity of the sample. It is also preferable to perform the air suction and introduce water for preventing the sample from spreading to the tip of the sample nozzle.
In the present embodiment, in the case of the open type sample container 15, the volume V10 of the sample 92 and the volumes V3 and V4 of the system waters 88 and 90 do not change, and therefore, a minute amount of sample can be dispensed with high accuracy regardless of whether the sample container 15 is open or closed.
< second embodiment >
A second embodiment of the present invention will be described in detail with reference to fig. 6.
The present embodiment is configured to supply a reagent for sample analysis instead of supplying system water to the liquid supply unit in the first embodiment.
Fig. 6 is a vertical sectional view schematically showing the cleaning tank, the liquid supply unit, and the water droplet removing unit in the present embodiment. In the drawings, the same members as those of the first embodiment are denoted by the same reference numerals, and description thereof is omitted.
As shown in fig. 6, the cleaning tank 14 is provided with a cleaning nozzle 73, and the cleaning nozzle 73 cleans the sample nozzle 12a by discharging system water 74 stored in a water tank 81 and supplied by a pump 79 as cleaning water. Further, a solenoid valve 77 for opening and closing (switching between flow and cutoff) a pipe is provided in a pipe connecting the pump 79 and the cleaning nozzle 73. In washing tank 14, the washing water discharged from washing nozzle 73 passes through the washing position where sample nozzle 12a is washed, and is discarded to a waste liquid tank (not shown) through a waste liquid port 78 provided below.
The reagent 174 stored in the reagent cartridge 181 is supplied to the liquid supply unit 171 by the pump 179, and an electromagnetic valve 175 for opening and closing the line (switching between flow and cutoff) is provided in a line connecting the liquid supply unit 171 and the pump 179. The liquid supply section 171 is disposed adjacent to the cleaning tank 14, and emits a part of the reagent 174 from a discharge section 171a provided on the cleaning tank 14 side of the liquid supply section 171 to a cleaning position of the cleaning tank 14.
The water droplet removing unit 72 is connected to a vacuum pump 80, and a solenoid valve 76 for opening and closing (switching between flow and interruption) a pipe is provided in the pipe connecting the water droplet removing unit 72 and the vacuum pump 80. In the water droplet removing unit 72, the water droplets sucked from the outer wall of the sample nozzle 12a are discarded to a waste liquid tank (not shown) via the vacuum pump 80.
Step S170 in fig. 5 is a substitution with a reagent, and the other structure is the same as that of the first embodiment.
In the present embodiment configured as described above, the same effects as those of the first embodiment can be obtained.
The present invention is not limited to the above embodiments, and includes various modifications. For example, the above embodiments are described to facilitate understanding of the present invention, and are not necessarily limited to having all of the described configurations.
For example, numerical values and the like are merely examples and are not limited thereto. Although the case where the tip of the sample nozzle 12a slightly contacts the bottom surface of the reaction vessel 2 when the sample is discharged has been described, the tip may not contact the bottom surface. The bottom surface and the tip of the sample nozzle are physically connected by contact, which contributes to improvement in reliability of solving the problem of carry-back.
Description of the symbols
1-reaction plate; 2-a reaction vessel; 3, a cleaning mechanism; 4-a spectrophotometer; 5. 6, a stirring mechanism; 7. 8-reagent dispensing mechanism; 7a, 8 a-reagent nozzle; 9-reagent tray; 10-reagent bottle; 11 — a first sample dispensing mechanism; 11 a-sample nozzle; 12 — a second sample dispensing mechanism; 12 a-sample nozzle; 14, cleaning a tank; 15-sample container; 16-sample holder; 17-a sample conveying mechanism; 18-pumps for reagents; 19-pump for sample; 20-a pump for cleaning; 21-a control section; 30. 31-a cleaning tank; 41-arm drive mechanism; 42-arm; 51-a syringe pump; 51 a-syringe pump drive mechanism; 52. 75-77, 175-solenoid valves; 53. 79, 179-pump; 71. 171 — liquid supply; 71a, 171 a-discharge section; 72-water droplet removing part; 73-cleaning the nozzle; 74. 88, 89, 90-system water; 80-vacuum pump; 81-water tank; 82-water drops; 83-air saving; 84. 85, 92-sample; 86-a cover member; 91-air; 94-waste; 181-kit; 100 — automated analyzer.

Claims (10)

1. An automatic analyzer is characterized by comprising:
a sample dispensing mechanism having a sample nozzle for dispensing a sample in a sample container to a reaction vessel by sucking and discharging the sample to be analyzed;
a washing tank for washing the sample nozzle with washing water discharged from a washing nozzle; and
a control unit for controlling the sample dispensing mechanism to execute: a sample suction process of inserting the sample nozzle into the sample container to suck the sample in the sample container; a liquid suction process of detaching the sample nozzle from the sample container after the sample suction process, moving the sample nozzle to a cleaning position of the cleaning tank, cleaning an outer side of the sample nozzle by the cleaning nozzle, and sucking a liquid through the sample nozzle; and a discharge process of discharging the liquid and a part of the sample from the sample nozzle to the empty reaction vessel in this order,
in the liquid suction process, the cleaning liquid discharged from the cleaning nozzle is sucked as a liquid through the sample nozzle.
2. The automatic analysis device according to claim 1,
the control unit controls the sample dispensing mechanism to perform an air suction process such that an air suction process is performed by the sample nozzle after the liquid suction process,
in the discharge process, the air, the liquid, and a part of the sample are discharged from the sample nozzle in this order.
3. The automatic analysis device according to claim 1,
the sample includes whole blood or previously hemolyzed manual hemolysis,
when the sample is whole blood, the control unit controls the sample dispensing mechanism to perform the sample suction process, the liquid suction process, and the discharge process,
when the sample is manually hemolyzed, the control unit controls the sample dispensing mechanism to discharge a part of the sample to the empty reaction vessel without performing the liquid suction process.
4. The automatic analysis device according to claim 1,
the sample container is a closed type sample container having an opening at an upper portion thereof closed by a lid member,
the sample nozzle is formed to penetrate the lid member.
5. The automatic analysis device according to claim 1,
further comprising a spectrophotometer for measuring the absorbance of a reaction solution between a sample and a reagent,
the spectrophotometer measures absorbance of a reaction solution generated by discharging a reagent into the reaction container from which the liquid and a part of the sample are discharged.
6. An automatic analyzer is characterized by comprising:
a sample dispensing mechanism having a sample nozzle for dispensing a sample in a sample container to a reaction vessel by sucking and discharging the sample to be analyzed;
a washing tank for washing the sample nozzle with washing water discharged from a washing nozzle;
a control unit for controlling the sample dispensing mechanism to execute: a sample suction process of inserting the sample nozzle into the sample container to suck the sample in the sample container; a liquid suction process of detaching the sample nozzle from the sample container after the sample suction process, moving the sample nozzle to a cleaning position of the cleaning tank, cleaning an outer side of the sample nozzle by the cleaning nozzle, and sucking a liquid through the sample nozzle; and a discharge process of discharging the liquid and a part of the sample from the sample nozzle to the empty reaction vessel in the order of the liquid and a part of the sample; and
a liquid supply unit for storing the liquid sucked by the liquid suction process,
the control unit controls the sample dispensing mechanism to perform a cleaning water introduction process of introducing the cleaning water discharged from the cleaning nozzle into the sample nozzle between the sample suction process and the liquid suction process,
in the liquid suction process, the liquid in the liquid supply part is sucked through the sample nozzle in a state where the cleaning water is introduced into the sample nozzle,
in the discharge process, the liquid, the washing water, and a part of the sample are discharged from the sample nozzle in this order,
the liquid is system water or a reagent used for analyzing the sample.
7. An automatic analyzer is characterized by comprising:
a sample dispensing mechanism having a sample nozzle for dispensing a sample in a sample container to a reaction vessel by sucking and discharging the sample to be analyzed;
a washing tank for washing the sample nozzle with washing water discharged from a washing nozzle;
a control unit for controlling the sample dispensing mechanism to execute: a sample suction process of inserting the sample nozzle into the sample container to suck the sample in the sample container; a liquid suction process of detaching the sample nozzle from the sample container after the sample suction process, moving the sample nozzle to a cleaning position of the cleaning tank, cleaning an outer side of the sample nozzle by the cleaning nozzle, and sucking a liquid through the sample nozzle; and a discharge process of discharging the liquid and a part of the sample from the sample nozzle to the empty reaction vessel in the order of the liquid and a part of the sample; and
a liquid supply unit for storing the liquid sucked by the liquid suction process,
the control unit controls the sample dispensing mechanism such that: performing a cleaning water introduction process of introducing the cleaning water discharged from the cleaning nozzle into the sample nozzle between the sample suction process and the liquid suction process; and performing an air suction process of sucking air through the sample nozzle after the liquid suction process,
in the liquid suction process, the liquid in the liquid supply part is sucked through the sample nozzle in a state where the cleaning water is introduced into the sample nozzle,
in the discharge process, the air, the liquid, the washing water, and a part of the sample are discharged from the sample nozzle in this order,
the liquid is system water or a reagent used for analyzing the sample.
8. An automatic analyzer is characterized by comprising:
a sample dispensing mechanism having a sample nozzle for dispensing a sample in a sample container to a reaction vessel by sucking and discharging the sample to be analyzed;
a washing tank for washing the sample nozzle with washing water discharged from a washing nozzle;
a liquid supply unit that stores the liquid sucked by the sample nozzle; and
a control unit for controlling the sample dispensing mechanism to perform: a sample suction process of inserting the sample nozzle into the sample container and sucking the sample in the sample container; a cleaning water introduction process of detaching the sample nozzle from the sample container after the sample suction process, moving the sample nozzle to a cleaning position of the cleaning tank, cleaning an outer side of the sample nozzle by the cleaning nozzle, and introducing cleaning water discharged from the cleaning nozzle into the sample nozzle; a liquid suction process of moving the sample nozzle to the liquid supply unit after the cleaning water introduction process and sucking liquid through the sample nozzle; an air suction process of performing air suction through the sample nozzle after the liquid suction process; a discharge process of discharging the air, the liquid, the washing water, and a part of the sample from the sample nozzle to the empty reaction container in this order,
the liquid is system water or a reagent used for analyzing the sample.
9. An analysis method in an automatic analyzer having a sample dispensing mechanism including a sample nozzle for dispensing a sample in a sample container into a reaction container by sucking and discharging the sample to be analyzed,
the analysis method is characterized by comprising:
a sample suction processing step of inserting the sample nozzle into the sample container and sucking the sample in the sample container;
a liquid suction processing step of separating the sample nozzle from the sample container, moving the sample nozzle to a cleaning position in a cleaning tank, cleaning the outside of the sample nozzle with a cleaning nozzle, and sucking a liquid through the sample nozzle after the sample suction processing step; and
a discharge treatment step of discharging the liquid and a part of the sample from the sample nozzle to the empty reaction vessel in the order of the liquid and a part of the sample,
a cleaning water introduction processing step of introducing cleaning water into the sample nozzle between the sample suction processing step and the liquid suction processing step,
an air suction processing step of performing air suction through the sample nozzle after the liquid suction processing step,
in the discharge treatment step, the air, the liquid, the washing water, and a part of the sample are discharged from the sample nozzle in this order,
the liquid is system water or a reagent used for analyzing the sample.
10. The analytical method of claim 9,
the method further comprises a step of measuring the absorbance of a reaction solution of a part of the sample and the reagent.
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